This project focuses on leiomyomata (fibroids) and endometriosis and examines factors related to their pathogenesis, diagnosis and/or potential treatment. We have hypothesized that gene expression is different in fibroids and myometrium, and these differences may suggest pathophysiologic etiologies. We have evaluated samples obtained from women undergoing routine hysterectomy for fibroids using the 33,000 gene Affymetrix array and subsequent validation studies evaluating messenger RNA and protein. These data showed mild Frizzled-2 overexpression and robust CD-24 overexpression. We are currently evaluating the ability of the progesterone receptor modulator CDB-2914 to shrink fibroid tumors. To evaluate the actions of CDB-2914 as a potential therapeutic agent, we gave a single midluteal dose (1 to 100 mg) of the agent to normally cycling women. At 200 mg only, women had early bleeding. There was no effect on other endocrine parameters and no toxicity. An ongoing randomized, double-blind, placebo-controlled phase II study evaluates whether surgical excision of endometriosis followed by daily administration of raloxifene for six months reduces pain for a longer time than surgery alone. In women participating in this study, we evaluated the utility of fat suppressed magnetic resonance imaging (MRI) for the diagnosis of endometriosis compared to surgical inspection and biopsy. The MRI detected fewer endometriosis lesions than histopathology or laparoscopy. MRI detected biopsy-proven endometriosis in 69% of women with the disorder. We also correlated clinical and pathologic diagnosis in suspected endometriosis lesions excised at laparoscopy, finding that white, mixed color lesions, endometriomas, and larger lesions by depth or width were more likely to be histologically confirmed endometriosis than smaller, black or red lesions. We evaluated a woman with amenorrhea caused by an LH secreting pancreatic tumor, and showed that increased levels of LH did not cause hyperandrogenism in this setting.